CVD Genetic Predispositions and Genomic Signatures Principal Investigator: Cam Patterson, MD, MBA Cardiovascular diseases (CVD) are the most common cause of morbidity and mortality in the US, accounting for 1/2 of all deaths and health care expenditures. Their incidence is magnified in minority populations and in lower socioeconomic strata. Our proposed clinical research plan targets the cardiovascular diseases that disproportionately afflict underserved and disadvantaged North Carolinians, utilizing a systems approach to develop models that will integrate clinical data with datasets derived from clinical genomics and other inductive, highly detailed methods. To this end, we have developed an approach we refer to as the SAMARA (Supporting A Multidisciplinary Approach to Research in Atherosclerosis) Project that applies recent, major advances in biomedical and computational sciences at UNC to develop deeper understanding of human CVD. Using a combination of high-throughput data collection and computational data mining and model building, we have tested this systems approach on 200 subjects at high risk for CVD. We identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Having established and tested this integrative approach, we are now prepared to expand our studies into the community by using this methodology to: 1). Determine the prevalence of genomic risk signatures in high-risk community populations using genome-wide SNP analysis; 2). Develop novel genomic models incorporating high-risk features in this population; 3). Determine whether genomic signatures can be used to predict responsiveness to interventions that underiie CVD disparities.